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Effects Of The Selective Gsk3b Inhibitor, Tideglusib, On Ethanol Consumption, Anxiety-Like Behavior, Taste Preference, And Downstream Proteins, Sam Gottlieb, Douglas Bledsoe, Jessica L. Maltman, Alanna Morgan, Jennifer T. Wolstenholme, Michael F. Miles Jan 2022

Effects Of The Selective Gsk3b Inhibitor, Tideglusib, On Ethanol Consumption, Anxiety-Like Behavior, Taste Preference, And Downstream Proteins, Sam Gottlieb, Douglas Bledsoe, Jessica L. Maltman, Alanna Morgan, Jennifer T. Wolstenholme, Michael F. Miles

Graduate Research Posters

Background: We have shown modulations in glycogen synthase kinase 3 beta (GSK3B) abundance or activity regulate ethanol consumption, suggesting potential as a therapeutic target for alcohol use disorder (AUD). Here we report the GSK3B inhibitor tideglusib’s actions on ethanol consumption, basal behaviors, and modulation of GSK3B targets.

Methods: C57BL/6J males and females received i.g. 200mg/kg tideglusib, except drinking-in-the-dark (males;100mg/kg i.p.). Drinking-in-the-dark (DID): Mice given 20% ethanol 4-hours, 4-days/week x 3 weeks and then i.p. tideglusib or vehicle x 4 days in a Latin Square design with ethanol consumption measured daily. Light/Dark Box: Mice gavaged with tideglusib or vehicle …


Selective Gsk3b Deletion In Camk2a+ Forebrain Neurons Or Inhibition Via Tideglusib, Decreases Ethanol Consumption In C57bl/6j Mice, Sam Gottlieb, Andrew D. Van Der Vaart, Brennen O'Rourke, Michael F. Miles Jan 2021

Selective Gsk3b Deletion In Camk2a+ Forebrain Neurons Or Inhibition Via Tideglusib, Decreases Ethanol Consumption In C57bl/6j Mice, Sam Gottlieb, Andrew D. Van Der Vaart, Brennen O'Rourke, Michael F. Miles

Graduate Research Posters

Purpose: We previously identified glycogen synthase kinase-3 beta (Gsk3b) as a central member of a gene network highly regulated by acute ethanol in medial prefrontal cortex (mPFC) and associated with risk for alcohol dependence in humans. Further, we have demonstrated modulation of Gsk3b alters ethanol consumption in rodent models. GSK3B could thus represent a potential new therapeutic target for the treatment of alcohol use disorder (AUD). Here, we investigate the mechanisms of Gsk3b action in ethanol consumption and report preclinical evidence for the selective GSK3B inhibitor, tideglusib, as a therapeutic agent for AUD.

Methods: (1) Selective Cre-induced Gsk3b …